rs1432812

Variant names:

• chr5-155847690-A-G
• rs1432812
• XM_017009724.2:c.-208+118700A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000755060.1(ENSG00000298352):​n.509-6859A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,154 control chromosomes in the GnomAD database, including 3,686 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3686 hom., cov: 32)
• Consequence: ENSG00000298352 ENST00000755060.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338
• Publications: 4 publications found

Genes affected

SGCD (HGNC:10807): (sarcoglycan delta) The protein encoded by this gene is one of the four known components of the sarcoglycan complex, which is a subcomplex of the dystrophin-glycoprotein complex (DGC). DGC forms a link between the F-actin cytoskeleton and the extracellular matrix. This protein is expressed most abundantly in skeletal and cardiac muscle. Mutations in this gene have been associated with autosomal recessive limb-girdle muscular dystrophy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene. [provided by RefSeq, Jul 2008]

SGCD Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2F

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Myriad Women's Health, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• dilated cardiomyopathy 1L

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ENSG00000298352 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000755060.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000298352	ENST00000755060.1		n.509-6859A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28840 AN: 152036 Hom.: 3679 Cov.: 32

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.212

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.190 AC: 28854 AN: 152154 Hom.: 3686 Cov.: 32 AF XY: 0.193 AC XY: 14380 AN XY: 74380

African (AFR) AF: 0.0533 AC: 2214 AN: 41546

American (AMR) AF: 0.403 AC: 6160 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3472

East Asian (EAS) AF: 0.270 AC: 1399 AN: 5176

South Asian (SAS) AF: 0.131 AC: 633 AN: 4814

European-Finnish (FIN) AF: 0.236 AC: 2491 AN: 10568

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14618 AN: 67992

Other (OTH) AF: 0.210 AC: 443 AN: 2110

Alfa AF: 0.211 Hom.: 12947

Bravo AF: 0.201

Asia WGS AF: 0.177 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.5
DANN	Benign	0.76
PhyloP100		0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1432812;

hg19: chr5-155274700;